Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 11, 2023

Abstract Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed circumvent tumor plasticity, including epigenetic modifications, regulation transcription factors, activation suppression key signaling pathways, as well modification environment. Epithelial-to-mesenchymal transition, stem formation also serve roads towards Corresponding treatment strategies recently developed that either target plasticity-related employ combination treatments. In this review, we delineate plasticity its manipulation evasion from therapy. We discuss non-genetic drug-induced various types tumors provide insights into contribution acquired drug resistance. New therapeutic such inhibition reversal are presented. multitude clinical trials ongoing worldwide with intention improving outcomes. These advances direction for developing novel therapy regimens

Language: Английский

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Glioblastoma Therapy: Past, Present and Future

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2529 - 2529

Published: Feb. 21, 2024

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians researchers, no significant improvement in survival has achieved since Stupp protocol became standard care (SOC) 2005. Despite multimodality treatments, recurrence is almost universal with rates under 2 years after diagnosis. Here, we discuss recent progress our understanding GB pathophysiology, particular, importance glioma stem cells (GSCs), tumor microenvironment conditions, epigenetic mechanisms involved growth, aggressiveness recurrence. The discussion on therapeutic strategies first covers SOC treatment targeted therapies that shown to interfere different signaling pathways (pRB/CDK4/RB1/P16

Language: Английский

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Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 25, 2023

Glioblastoma multiforme (GBM) is the most common and fatal primary malignant central nervous system tumor in adults. Although there are multiple treatments, median survival of GBM patients unsatisfactory, which has prompted us to continuously investigate new therapeutic strategies, including drugs drug delivery approaches. Ferroptosis, a kind regulated cell death (RCD), been shown be dysregulated various tumors, GBM. Fatostatin, specific inhibitor sterol regulatory element binding proteins (SREBPs), involved lipid cholesterol synthesis antitumor effects variety tumors. However, effect fatostatin not explored field ferroptosis or In our study, through transcriptome sequencing, vivo experiments, vitro we found that induces by inhibiting AKT/mTORC1/GPX4 signaling pathway glioblastoma. addition, inhibits proliferation EMT process AKT/mTORC1 pathway. We also designed p28-functionalized PLGA nanoparticle loaded with fatostatin, could better cross blood-brain barrier (BBB) targeted Our research identified unprecedented presented novel drug-targeted vehicle capable penetrating BBB

Language: Английский

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Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 18, 2024

Abstract The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal conditions, the is meticulously regulated. However, aberrant activation of this downstream target genes can occur due to mutations key components pathway, epigenetic modifications, crosstalk with other pathways. Consequently, these dysregulations contribute significantly tumor initiation progression. Therapies targeting transduction have exhibited promising prospects potential for treatment. An increasing number medications are continuously being developed validated. This comprehensive review aims summarize latest advances our understanding played by carcinogenesis targeted therapy, providing valuable insights into acknowledging current opportunities challenges associated cancer research

Language: Английский

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Regulation of Autophagy via Carbohydrate and Lipid Metabolism in Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2195 - 2195

Published: April 7, 2023

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian that digests damaged organelles misfolded proteins lysosomal degradation, is closely associated with metabolism cells, acting as meter cellular ATP levels. In this review, we discuss the glycolytic biosynthetic pathways their impact on carcinogenesis autophagy pathway. addition, these metabolic lung cancer.

Language: Английский

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Digging the intercellular crosstalk via extracellular vesicles: May exosomes be the drug delivery solution for target glioblastoma?

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 358, P. 98 - 115

Published: April 29, 2023

Glioblastoma (GBM) is an adult's most aggressive brain tumor. The advances in molecular pathology and cell signaling pathways have deepened researchers' understanding of intercellular communication mechanisms that can induce tumor progression, namely the release extracellular vesicles. Exosomes are small vesicles various biological fluids released by almost all cells, thus carrying biomolecules specific to their parental cell. Several pieces evidence indicate exosomes mediate microenvironment cross blood-brain barrier (BBB), valuable tools for diagnostic therapeutic applications under scope diseases such as tumors. This review aims resume several characteristics interplay between glioblastoma exosomes, describing highlight studies demonstrate role GBM potential non-invasive diagnoses approaches, namely, nanocarriers drug or gene delivery cancer vaccines.

Language: Английский

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Temozolomide, Simvastatin and Acetylshikonin Combination Induces Mitochondrial-Dependent Apoptosis in GBM Cells, Which Is Regulated by Autophagy

Biology, Journal Year: 2023, Volume and Issue: 12(2), P. 302 - 302

Published: Feb. 14, 2023

Glioblastoma multiforme (GBM) is one of the deadliest cancers. Temozolomide (TMZ) most common chemotherapy used for GBM patients. Recently, combination strategies have had more effective antitumor effects and focus on slowing down development resistance. A TMZ cholesterol-lowering medications (statins) currently under investigation in vivo clinical trials. In our current investigation, we a triple-combination therapy TMZ, Simvastatin (Simva), acetylshikonin, investigated its apoptotic mechanism cell lines (U87 U251). We viability, apoptosis, reactive oxygen species, mitochondrial membrane potential (MMP), caspase-3/-7, acridine orange (AO) immunoblotting autophagy assays. Our results showed that TMZ/Simva/ASH induced significantly apoptosis compared to Simva, ASH, TMZ/Simva treatments cells. Apoptosis via treatment damage (increase ROS, decrease MMP) caspase-3/7 activation both lines. Compared all single treatment, increased positive acidic vacuole organelles. further confirmed increase AVOs during was due partial inhibition flux (accumulation LC3β-II p62 degradation) also TMZ/Simva/ASH-induced death depended flux, as Finally, potentially depends an Bax expression might open new avenues GBM, but investigations are required better identification mechanisms.

Language: Английский

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The obesity-autophagy-cancer axis: Mechanistic insights and therapeutic perspectives

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 99, P. 24 - 44

Published: Feb. 1, 2024

Autophagy, a self-degradative process vital for cellular homeostasis, plays significant role in adipose tissue metabolism and tumorigenesis. This review aims to elucidate the complex interplay between autophagy, obesity, cancer development, with specific emphasis on how obesity-driven changes affect regulation of autophagy subsequent implications risk. The burgeoning epidemic obesity underscores relevance this research, particularly given established links various cancers. Our exploration delves into hormonal influence, notably INS (insulin) LEP (leptin), interactions. Further, we draw attention latest findings molecular factors linking cancer, including changes, altered metabolism, secretory autophagy. We posit that targeting modulation may offer potent therapeutic approach obesity-associated pointing promising advancements nanocarrier-based targeted therapies modulation. However, also recognize challenges inherent these approaches, concerning their precision, control, dual roles can play cancer. Future research directions include identifying novel biomarkers, refining therapies, harmonizing approaches precision medicine principles, thereby contributing more personalized, effective treatment paradigm obesity-mediated

Language: Английский

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Revolutionizing Glioblastoma Treatment: A Comprehensive Overview of Modern Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5774 - 5774

Published: May 26, 2024

Glioblastoma is the most common malignant primary brain tumor in adult population, with an average survival of 12.1 to 14.6 months. The standard treatment, combining surgery, radiotherapy, and chemotherapy, not as efficient we would like. However, current possibilities are no longer limited therapies due rapid advancements biotechnology. New methods enable a more precise approach by targeting individual cells antigens overcome cancer. For treatment glioblastoma, these gamma knife therapy, proton beam tumor-treating fields, EGFR VEGF inhibitors, multiple RTKs PI3K pathway inhibitors. In addition, increasing understanding role immune system tumorigenesis ability identify tumor-specific helped develop immunotherapies GBM cells, including CAR-T, CAR-NK dendritic checkpoint Each described has its advantages disadvantages faces problems, such inefficient crossing blood-brain barrier, various neurological systemic side effects, escape mechanism tumor. This work aims present modern treatments glioblastoma.

Language: Английский

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Immune checkpoints between epithelial-mesenchymal transition and autophagy: A conflicting triangle

Cancer Letters, Journal Year: 2024, Volume and Issue: 585, P. 216661 - 216661

Published: Feb. 2, 2024

Inhibitory immune checkpoint (ICP) molecules are pivotal in inhibiting innate and acquired antitumor responses, a mechanism frequently exploited by cancer cells to evade host immunity. These evasion strategies contribute the complexity of progression therapeutic resistance. For this reason, ICP have become targets for drugs, particularly monoclonal antibodies, collectively referred as inhibitors (ICI), that counteract such cancer-associated suppression restore responses. Over last decade, however, it has clear tumor cell-associated ICPs can also induce cell-intrinsic effects, particular epithelial-mesenchymal transition (EMT) macroautophagy (hereafter autophagy). Both these processes profound implications metastasis drug responsiveness. This article reviews positive or negative cross-talk undergo with autophagy EMT. We discuss upregulated response same stimuli Moreover, themselves, when overexpressed, an EMT-inducing stimulus. As regards autophagy, been shown either stimulate inhibit while itself up- downregulate expression ICPs. dynamic equilibrium extends autophagy-apoptosis axis, further emphasizing complexities cellular Eventually, we delve into intricate balance between apoptosis, elucidating its role broader interplay dynamics influenced In final part article, speculate about driving forces underlying contradictory outcomes reciprocal, inhibitory, stimulatory effects ICPs, EMT, autophagy. A conclusive identification may allow achieve improved using combinations ICIs compounds acting on EMT and/or Prospectively, translate increased broadened efficacy compared what is currently achieved ICI-based clinical protocols.

Language: Английский

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